A photoacoustic tomography (hereinafter sometimes abbreviated as “PAT”) apparatus has been known as one apparatus for visualizing information on the inside of a living body. In measurement involving using the PAT apparatus, the intensity of a photoacoustic signal emitted from a substance (light absorber) that absorbs light in a body to be measured when the body to be measured is irradiated with light and the time point at which the signal occurs are measured, whereby an image in which a substance distribution in the body to be measured is subjected to an operation can be obtained.
Any light absorber can be used as the light absorber as long as the light absorber absorbs light in the living body to emit an acoustic wave. For example, a blood vessel or malignant tumor in a human body can be used as the light absorber. In addition, a molecule such as indocyanine green (hereinafter sometimes abbreviated as “ICG”) can be administered to the body to be utilized as a contrast agent. ICG can be suitably used as a contrast agent in the PAT apparatus because ICG has a small influence when administered to the human body and absorbs light in a near-infrared wavelength region, which has high permeability for the living body, well. It should be noted that the term “ICG” as used herein refers to a compound represented by the following structure.
It should be noted that a counter ion may not be Na+ and an arbitrary counter ion such as H+ or K+ can be used.
In addition, ICG has been used in fluorescence imaging because the compound absorbs near-infrared light to emit near-infrared fluorescence. In other words, ICG is administered to a body to be measured, and after a certain time period, a fluorescence signal emitted from ICG that absorbs light in the body to be measured when the body is irradiated with light from the outside is measured, whereby an ICG distribution in the body to be measured can be imaged. For example, a sentinel lymph node can be visualized.
However, it has been known that the half-life of ICG in blood is about several minutes, which is extremely short.
In view of the foregoing, Non Patent Literature 1 reports an example in which the fluorescence in vivo imaging of a lymph node or a tumor is performed by conjugating a hydrophilic derivative of ICG described above (ICG-OSu) to hyaluronic acid having a molecular weight of 40,000 as a natural polysaccharide to form nanoparticles each having an average particle diameter of 188 nm. The report shows that the derivative remains in blood for a long time period as compared to ICG alone and accumulates in the lymph node or the tumor.
Patent Literature 1 reports an example in which the fluorescence in vivo imaging of a lymph node is performed by conjugating IR783 as a hydrophilic near-infrared dye to hyaluronic acid.
Patent Literature 2 reports a hyaluronic acid derivative to which fluorescein has been covalently conjugated, and the derivative has been used in a method of measuring the activity of a glycosaminoglycan degrading enzyme.
Non Patent Literature 2 reports a nanoparticle of a hyaluronic acid derivative obtained by conjugating polyethylene glycol (hereinafter sometimes abbreviated as “PEG”) to hydrophobized hyaluronic acid having a molecular weight of 2,500,000. Further, the literature reports a nanoparticle of a hydrophobized hyaluronic acid derivative in which PEG and a hydrophilic near-infrared dye Cy5.5 are conjugated, the nanoparticle being obtained by covalently conjugating the near-infrared dye to the foregoing nanoparticle, and reports an example of fluorescence in vivo imaging.